E-Cadherin endocytosis in morphogenesis: recycling and growth factor induced uptake.

E-钙粘蛋白是一种细胞-细胞粘附蛋白，在所有上皮细胞中表达，在发育过程中建立细胞极性和组织模式中起重要作用。在成人中，E-钙粘蛋白的功能是维持上皮完整性。E-钙粘蛋白也是一种重要的肿瘤抑制因子，保护细胞免受转移转化。我们早期的研究表明，E-钙粘蛋白是不断移动，或贩运，从上皮细胞的表面。细胞表面E-钙粘蛋白的内吞作用或内化用于调节其在粘附中的作用。最近，我们和其他人已经表明，E-钙粘蛋白是内吞响应生长因子，结合活化的生长因子受体本身。E-钙粘蛋白可以影响这些受体酪氨酸激酶的运输和信号传导。这种联合内吞作用是同时下调细胞粘附和激活细胞生长和运动的信号传导的优雅机制。上皮细胞在组织形成或形态发生过程中的生长和分化主要依赖于这些内吞途径。我们的研究旨在确定参与E-cadherin受体内吞作用的内体和细胞机制，此外，我们还将寻求初步发现，表明在不同生长因子的要求下，E-cadherin内吞有不同的途径和命运。我们将研究上皮囊肿形成和囊肿的滋养过程中的内吞作用，作为哺乳动物形态发生的体外模型。这些研究将为理解上皮细胞形态发生过程中E-钙粘蛋白在粘附和生长因子信号传导中的作用提供重要和新颖的信息。最终，这些发现将与上皮发育和癌症预防有关。

E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.